This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sustained SIV infection of the CNS depends on macrophage-tropic (M-tropic) strains that are often easily neutralizable. Concomitantly, the CNS is often thought of as an immunologically privileged site that fosters replication of M-tropic quasispecies. Yet, there are limited data addressing the intrathecal antibody response or the role of the humoral response in general to control M-tropic strains. We investigated the temporal course of the intrathecal neutralizing activity and found an inverse relationship between the magnitude of neutralization and the prevalence of M-tropic populations. These studies suggest a role for the humoral response in the suppression of M-tropic viral species in the CNS in experimental SIV infection.